While patients with cancer often have a reduced capacity to mount cellular immune responses, patients with multiple myeloma and mice bearing plasmacytomas often exhibit a unique pattern of immunodeficiency: Hosts of plasma cell tumors often produce gram quantities of a monoclonal immunoglobulin, but are unable to synthesize normal immunoglobulins, particularly in response to a primary challenge with antigen. These tumor hosts maintain normal T cell functions. Plasma cell tumors therefore seem to exert a very strict regulatory effect on precursors of immunoglobulin producing cells. These findings suggest that hosts of plasma cell tumors exhibit two functions characteristic of normal plasma cells: The production of immunoglobulin and the regulation of the maturation of the precursors of antibody forming cells. One of our objectives, then, is to document this postulated regulatory function of plasma cells by determining if a similar immunodeficiency syndrome characterizes mice stimulated to make homogeneous antibodies. In addition we propose to extend our previous work in which we demonstrated both a soluble and a cellular mediator of B cell regulation in plasmacytoma-bearing mice. These studies are thus designed to elucidate both the reason for the immunodeficiency syndrome characteristic of human and murine hosts of plasma cell tumors and to illuminate an immunoregulatory pathway, heretofore undescribed, by which plasma cells regulate the antibody response of other B lymphocytes.